VCV000066087.1 - ClinVar

NC_000024.9:g.730550_778092del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000024.9:g.730550_778092del

Variation ID: 66087 Accession: VCV000066087.1

Type and length

Deletion, 47,543 bp

Location

Cytogenetic: Yp11.32 Xp22.33 X: 730550-778092 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 9, 2018	Nov 9, 2018	Jul 1, 2012

HGVS

Nucleotide	Protein	Molecular consequence
NC_000024.9:g.730550_778092del

Protein change

Other names

47.5-KB DEL, DOWNSTREAM ENHANCER

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 312865.0016 VarSome

Comment on variant

47.5-kb deletion downstream of the SHOX gene

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SHOX		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38	164	363

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Leri-Weill dyschondrosteosis	Pathogenic (1)	no assertion criteria provided	Jul 1, 2012	RCV000056322.4
SHOX-related short stature	Pathogenic (1)	no assertion criteria provided	Jul 1, 2012	RCV000056323.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 01, 2012)	no assertion criteria provided Method: literature only	LERI-WEILL DYSCHONDROSTEOSIS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000087491.2 First in ClinVar: Oct 18, 2013 Last updated: Nov 09, 2018	Publications: PubMed (1) PubMed: 22791839 Comment on evidence: Benito-Sanz et al. (2012) identified the same 47,543-bp deletion (chrX:700,549-748,093, GRCh37) in the pseudoautosomal region 1 (PAR1) downstream of the SHOX gene in 19 of … (more) Benito-Sanz et al. (2012) identified the same 47,543-bp deletion (chrX:700,549-748,093, GRCh37) in the pseudoautosomal region 1 (PAR1) downstream of the SHOX gene in 19 of 124 probands with Leri-Weill dyschondrosteosis (127300) (15.3%) and 11 of 576 probands with idiopathic short stature (300582) (1.9%). Eight evolutionarily conserved regions (ECRs) were identified within the deleted sequence, and all ECRs were evaluated for SHOX regulatory activity. Chromosome conformation capture assays in embryonic chicken limbs demonstrated that ECR1 interacts with a sequence close to or within the SHOX proximal promoter. Luciferase reporter assays confirmed that ECR1 operates as an orientation- and position-independent enhancer. (less)
Pathogenic (Jul 01, 2012)	no assertion criteria provided Method: literature only	SHORT STATURE, IDIOPATHIC, X-LINKED Affected status: not provided Allele origin: germline	OMIM Accession: SCV000087492.2 First in ClinVar: Oct 18, 2013 Last updated: Nov 09, 2018	Publications: PubMed (1) PubMed: 22791839 Comment on evidence: Benito-Sanz et al. (2012) identified the same 47,543-bp deletion (chrX:700,549-748,093, GRCh37) in the pseudoautosomal region 1 (PAR1) downstream of the SHOX gene in 19 of … (more) Benito-Sanz et al. (2012) identified the same 47,543-bp deletion (chrX:700,549-748,093, GRCh37) in the pseudoautosomal region 1 (PAR1) downstream of the SHOX gene in 19 of 124 probands with Leri-Weill dyschondrosteosis (127300) (15.3%) and 11 of 576 probands with idiopathic short stature (300582) (1.9%). Eight evolutionarily conserved regions (ECRs) were identified within the deleted sequence, and all ECRs were evaluated for SHOX regulatory activity. Chromosome conformation capture assays in embryonic chicken limbs demonstrated that ECR1 interacts with a sequence close to or within the SHOX proximal promoter. Luciferase reporter assays confirmed that ECR1 operates as an orientation- and position-independent enhancer. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer.	Benito-Sanz S	Journal of medical genetics	2012	PMID: 22791839

Text-mined citations for this variant ...

Record last updated Jun 11, 2022

ClinVar Genomic variation as it relates to human health

NC_000024.9:g.730550_778092del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...